Fujikawa M, Kamiike W, Hatanaka N, Shimizu S, Akashi A, Miyata M, Kurosawa K, Yoshida Y, Tagawa K, Matsuda H
First Department of Surgery, Osaka University Medical School, Japan.
J Surg Res. 1994 Nov;57(5):569-73. doi: 10.1006/jsre.1994.1184.
Changes in hepatic and biliary glutathione levels were studied in rat liver treated with tert-butyl hydroperoxide (t-BuOOH) and subjected to ischemia-reperfusion. Immediately after t-BuOOH administration, the oxidized glutathione (GSSG) values and reduced glutathione (GSSG/GSH) ratio in the bile increased dose-dependently and then returned to control level within 10 min, whereas the hepatic ATP level and bile flow rate were not affected by t-BuOOH at doses of up to 1.0 mmol/kg. These data suggested that the liver remains viable on treatment with up to 1.0 mmole/kg t-BuOOH, and that hepatocytes can rapidly dismute t-BuOOH at up to this dose. The hepatic GSH and GSSG levels did not vary appreciably during ischemia for 10 or 30 min or during subsequent reperfusion, but the GSSG/GSH ratio increased after ischemia for 30 min. The rate of bile flow and the biliary level of GSH decreased after ischemia for 30 min in proportion to the decrease in the hepatic ATP level. However, the biliary GSSG concentration did not vary on reperfusion, although GSSG secretion into the bile is also related to the hepatic ATP level. As a result, the GSSG/GSH ratio in the bile increased during reperfusion after ischemia for 30 min. This increased ratio is thought to reflect oxidation of hepatic GSH by hydroperoxide produced during reperfusion. The GSSG/GSH ratio in the bile after 30 min ischemia corresponded to that observed after a small dose (0.07 mmole/kg body wt) of t-BuOOH, which hepatocytes could dismute rapidly without loss of their viability.(ABSTRACT TRUNCATED AT 250 WORDS)
研究了叔丁基过氧化氢（t-BuOOH）处理并经历缺血再灌注的大鼠肝脏中肝和胆汁中谷胱甘肽水平的变化。给予t-BuOOH后，胆汁中氧化型谷胱甘肽（GSSG）值和谷胱甘肽氧化还原比（GSSG/GSH）呈剂量依赖性增加，然后在10分钟内恢复至对照水平，而在剂量高达1.0 mmol/kg时，肝ATP水平和胆汁流速不受t-BuOOH影响。这些数据表明，肝脏在高达1.0 mmol/kg t-BuOOH处理下仍保持存活，并且肝细胞在该剂量以下能够迅速歧化t-BuOOH。在缺血10或30分钟期间及随后的再灌注过程中，肝脏GSH和GSSG水平没有明显变化，但缺血30分钟后GSSG/GSH比增加。缺血30分钟后胆汁流速和胆汁中GSH水平与肝ATP水平下降成比例降低。然而，尽管GSSG分泌到胆汁中也与肝ATP水平有关，但再灌注时胆汁中GSSG浓度没有变化。因此，缺血30分钟后再灌注期间胆汁中GSSG/GSH比增加。这种增加的比例被认为反映了再灌注期间产生的氢过氧化物对肝GSH的氧化。缺血30分钟后胆汁中的GSSG/GSH比与小剂量（0.07 mmol/kg体重）t-BuOOH后观察到的比值相当，肝细胞能够迅速歧化该剂量的t-BuOOH而不丧失其活力。（摘要截短于250字）
